| Eligibility |
Inclusion Criteria:
1. Signed IRB-approved informed consent form that meets all criteria of current FDA
regulations.
2. Postmenopausal females aged 30-75 years inclusive. Postmenopausal is defined as
follows:
1. At least 6 months of spontaneous amenorrhea.
2. At least 6 weeks post-surgical bilateral oophorectomy, with or without
hysterectomy.
3. Hysterectomy without oophorectomy if of age that the Investigator believes would
have naturally reached 12 months of spontaneous amenorrhea if uterus had remained
intact.
3. Patients with a serum Follicle Stimulating Hormone (FSH) level of = 40 mIU/mL at
Screening.
4. Have = 5% superficial cells on vaginal smear cytology.
5. Have a vaginal pH > 5.0.
6. At least one of the following patient self-assessed moderate to severe symptoms of VVA
from the following list that is identified by the patient as being the most bothersome
to her:
- Vaginal Dryness
- Vaginal and/or Vulvar Irritation/Itching
- Dysuria
- Vaginal Pain associated with sexual activity
- Vaginal Bleeding associated with sexual activity (presence or absence)
- Provided that patient is currently sexually active and plans to remain so
throughout the study.
7. Have "Normal" Screening mammogram completed within 9 months before Screening in all
patients > 40 years old, with no findings that, in the opinion of the Investigator,
would indicate any suspicion of breast malignancy.
8. Normal clinical breast examination at Screening.
9. Patients with an intact uterus (including patients who underwent a partial
hysterectomy) must have a documented papanicolaou (PAP) smear conducted within the
previous 12 months with no findings that the Investigator believes would
contraindicate the use of topical vaginal estradiol.
10. Patients with an intact uterus should have vaginal ultrasonography results within 3
months before Screening to confirm an inactive endometrial lining, defined as
endometrial thickness < 4 mm.
Exclusion Criteria:
1. Significant history or current evidence of chronic infectious disease, system
disorder, organ disorder or other medical condition that in the Investigator's opinion
would place the study patient at undue risk by participation or could jeopardize the
integrity of the study evaluations.
2. Any clinically significant laboratory finding that, in the Investigator's opinion
would contraindicate the use of estradiol or compromise patient safety.
3. Patients with known concurrent vaginal infections including but not limited to:
Candida albicans, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhea or
Gardnerella vaginalis.
4. Patients with active vaginal herpes simplex infection or have had an outbreak within
30 days before the Screening.
5. Patients with known, suspected or current history of carcinoma of the breast.
6. Patients with baseline systolic blood pressure of > 150 mmHg and/or diastolic pressure
> 90 mmHg.
7. Any patient with past or current undiagnosed vaginal bleeding or significant risk
factors for endometrial cancer.
8. Any history of estrogen-dependent neoplasia (e.g., endometrial cancer).
9. Patients with known, suspected or current history of hormone dependent tumor.
10. History of acute thrombophlebitis or thromboembolic disorder.
11. Any prescription treatment for vaginal dryness/irritation within 14 days before
Screening or any over-the-counter or natural remedies within 7 days before Screening.
12. Any prescription treatment for bacterial or yeast infections within 30 days before
Screening.
13. Fasting triglyceride levels > 350 mg/dL.
14. History of radiation therapy or recent (within previous 6 weeks) surgical therapy to
the vaginal or cervical areas.
15. Any known or suspected allergies that, in the Investigator's opinion, would compromise
the safety of the patient.
16. Patients who have used vaginal hormonal products (rings, creams, gels) within the 7
days before Screening.
17. Patients who have used transdermal estrogen and/or progestin therapy within the 28
days before Screening.
18. Patients who have used oral estrogen and/or progestin therapy or intrauterine
progestin therapy within the 56 days before Screening.
19. Patients who have used progestin implants or estrogen alone injectable drug therapy
within the 3 month before Screening.
20. Patients who have used estrogen pellet therapy or progestin injectable drug therapy
within 6 months before Screening.
21. History of significant alcohol abuse within 1 year prior to Screening or regular use
of alcohol within 6 months before Screening (more than 14 units of alcohol per week [1
unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]).
22. History of significant drug abuse within 1 year prior to Screening, use of soft drugs
(such as marijuana) within 3 months before Screening, or hard drugs (such as cocaine,
phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine
derivatives) within 1 year before Screening.
23. Use within 30 days of Screening with known strong CYP3A4 inducers or inhibitors that,
in the opinion of the Investigator, may affect estrogen metabolism. Examples of strong
CYP3A4 inhibitors are macrolide antibiotics such as clarithromycin and telithromycin;
azole antifungals such as itraconazole and ketoconazole; antidepressants such as
nefazodone; and foods such as grapefruit or grapefruit juice. Examples of strong
CYP3A4 inducers are anticonvulsants such as carbamazepine and phenytoin; bactericidals
such as rifampin and rifabutin; and natural health products such as St. John's wort.
24. Inability to understand the requirements of the study and the relative information or
are unable or not willing to comply with the study protocol.
25. Receipt of any drug as part of a research study within 30 days before Screening.
26. Employees of the Investigator or research center or their immediate family members.
27. Patients who have participated in this study previously.
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